Publications by authors named "Kelei Gao"

17 Publications

  • Page 1 of 1

Current opinions on diagnosis and treatment of adenoid cystic carcinoma.

Oral Oncol 2022 Jul 2;130:105945. Epub 2022 Jun 2.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Anatomy Laboratory of Division of Nose and Cranial Base, Clinical Anatomy Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address:

Adenoid cystic carcinoma (ACC) is a rare malignant tumor derived mainly from the salivary glands, representing approximately 1% of all headandneck carcinomasand 10% of all salivary gland neoplasms. ACC displays a paradoxical behavioral combination of an indolent growth pattern but an aggressive progression, with local recurrence and distant metastasis. The propensity of ACC of the head and neck (ACCHN) for perineural invasion and its anatomical location, especially if it extends to the nasal cavity and paranasal sinuses, facilitates tumor involvement in the surrounding structures, such as the orbit, pterygopalatine fossa, Meckel'scave, and cavernous sinus, which can lead to skull base involvement and intracranial extension. Despite advances in molecular mechanisms and diagnostic imaging, ACC treatment remainschallenging due to the lack ofconsensuson treatment patterns. In this review, we aimed toprovideanupdatedinsight intothe understanding of ACCHN by focusing on clinical behavior, imaging diagnosis, pathological features, and therapeutic strategies. We reviewed the molecular mechanisms, especially in ACCHN with perineural invasion, and elaborated on treatment options, including chemotherapy, targeted therapies, and immunotherapy, to establish a comprehensive understanding of ACC to arrive at a policy for proper diagnosis, preoperative evaluation, and therapeutic strategies.
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http://dx.doi.org/10.1016/j.oraloncology.2022.105945DOI Listing
July 2022

Circulating C-X-C Motif Ligand 13 as a Biomarker for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With Chronic Allergic Rhinitis.

Front Pediatr 2022 4;10:872152. Epub 2022 May 4.

Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.

Background: C-X-C motif ligand 13 (CXCL13) and B cell-activating factor (BAFF) are proven to be involved in inflammatory diseases, but their role in allergic rhinitis (AR) remains unclear. The aim of this study was to investigate the role of serum CXCL13 and BAFF in AR and their clinical values as objective biomarkers to predict the efficacy of subcutaneous immunotherapy (SCIT).

Methods: We prospectively recruited 90 children with AR treated with SCIT and collected their serum specimens before SCIT. One-year follow-up was conducted for all patients, and they were categorized into effective and ineffective groups based on efficacy. The serum concentrations of CXCL13 and BAFF were detected and compared between the two groups. A validation cohort of 52 responders and 26 non-responders were further assessed for both cytokines and serum CXCL13 and BAFF levels were assayed by enzyme-linked immunosorbent assay (ELISA).

Results: Eighty children completed the follow-up schedule, and 56 children were categorized into the effective group and 24 children into the ineffective group. The serum levels of CXCL13 in the effective group were clearly higher than those in the ineffective group ( < 0.05). Receiver operating characteristic (ROC) curves revealed the potential values of CXCL13 as a biomarker in predicting the response of SCIT. Further, in the validation cohort, ELISA results demonstrated that serum CXCL13 levels were increased in responders than non-responders ( < 0.05). ROC curves showed good accuracy of serum CXCL13 in predicting the efficacy of SCIT.

Conclusion: Our discovery-validation study demonstrated that circulating CXCL13 might serve as a novel biomarker to predict the outcome of SCIT in childhood AR. The findings indicated that CXCL13 was involved in the pathological mechanisms of AR and made help to the fundamental therapeutic mechanism of SCIT.
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http://dx.doi.org/10.3389/fped.2022.872152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114669PMC
May 2022

Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling.

Front Immunol 2021 12;12:805404. Epub 2022 Jan 12.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.

Background: Subcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling.

Methods: We prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders.

Results: Sixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P < 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ.

Conclusion: Our discover-validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.
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http://dx.doi.org/10.3389/fimmu.2021.805404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789884PMC
February 2022

Preliminary Efficacy Report and Prognosis Analysis of Endoscopic Endonasal Nasopharyngectomy for Recurrent Nasopharyngeal Carcinoma.

Front Surg 2021 30;8:713926. Epub 2021 Aug 30.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.

Compared with radiotherapy, endoscopic endonasal nasopharyngectomy (EEN) is increasingly used to treat recurrent nasopharyngeal carcinoma (NPC) because of its good prognosis and mild complications. This study aims to investigate the efficacy of EEN in the treatment of recurrent NPC and factors affecting prognosis. This study included all patients who received EEN for recurrent nasopharyngeal carcinoma from April 2016 to April 2020. All operations were performed in Xiangya Hospital Central South University. The patient's 2-year overall survival (OS) rate, disease-free survival (DFS) rate and significant prognostic factors are reported. There were 38 (67.9%) males and 28 (32.1%) females, with a median age of 43 (range, 24-69 years).43 (76.8%) of the patients in our study were in advanced rT3-rT4 stage and 32 (74.4%) of the patients in the advanced stage had tumor growth closely related to the internal carotid artery (ICA). During a mean follow up period of 44 month (range 1-65 months) post-surgery. The 2-year OS rate was 48.6%, 2-year DFS rate was 42.6%. The 2-year OS rates of rT1-2 and rT3-4 recurrent NPC were 83.9 and 35.6%, respectively. The 2-year DFS rates of rT1-2 and rT3-4 recurrent NPC 76.2 and 56.3%. The advanced T stage were associated with a poor prognosis in terms of OS and DFS. Data indicate that T staging may be an independent prognostic factor for OS and DFS. Through proper preoperative evaluation, EEN is an alternative treatment option for advanced recurrent NPC that ensures a certain level of efficacy and is relatively safe with few complications. However, additional studies with long-term follow-up and a larger sample size are required.
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http://dx.doi.org/10.3389/fsurg.2021.713926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435752PMC
August 2021

Immune Microenvironment Change and Involvement of Circular RNAs in TIL Cells of Recurrent Nasopharyngeal Carcinoma.

Front Cell Dev Biol 2021 6;9:722224. Epub 2021 Aug 6.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.

Nasopharyngeal carcinoma is a malignant tumor that is highly prevalent in southern China and the Southeast Asian belt. Recent studies have shown that the T cells play important regulatory roles in tumorigenesis and progression. We test TIL cell of recurrent nasopharyngeal carcinoma and primary nasopharyngeal carcinoma cell. We found that T cell change in recurrent nasopharyngeal carcinoma and primary nasopharyngeal carcinoma cell. Based on GEO database, we selected differently expressed circRNAs in nasopharyngeal carcinoma tissues. qRTPCR show that some circRNAs also highly expressed in TIL cells. In conclusion, immune microenvironment changed in recurrent nasopharyngeal carcinoma. There is involvement of circular RNAs in this progress, with should be researched further.
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http://dx.doi.org/10.3389/fcell.2021.722224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377430PMC
August 2021

Comparing the Effectiveness of Endoscopic Surgeries With Intensity-Modulated Radiotherapy for Recurrent rT3 and rT4 Nasopharyngeal Carcinoma: A Meta-Analysis.

Front Oncol 2021 26;11:703954. Epub 2021 Jul 26.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, China.

Background: This meta-analysis aimed to compare the efficacy of intensity-modulated radiotherapy (IMRT) and endoscopic surgery (ES) for high T-stage recurrent nasopharyngeal carcinoma (NPC).

Methods: Relevant studies were retrieved in six databases from 02/28,2011 to 02/28,2021. The 2-year, 3-year, 5-year overall survival (OS) rates and 2-year disease-free survival (DFS) rates were calculated to compare the survival outcomes of the two treatments of IMRT and ES. Combined odds ratios (ORs) and 95% confidence interval (C Is) were measured as effect size on the association between high T-stage and 5-year OS rates.

Results: A total of 23 publications involving 2,578 patients with recurrent NPC were included in this study. Of these, 1611 patients with recurrent rT3-4 NPC were treated with ES and IMRT in 358 and 1,253 patients, respectively. The combined 2-year OS and 5-year OS rates for the two treatments were summarized separately, and the 2-year OS and 5-year OS rate for ES were 64% and 52%, respectively. The 2-year OS and 5-year OS rate for IMRT were 65% and 31%, respectively. The combined 2-year DFS rates of IMRT and ES were 60% and 50%, respectively. Combined ORs and 95% confidence intervals for 5-year survival suggest that ES may improve survival in recurrent NPC with rT3-4. In terms of complications, ES in the treatment of high T-stage recurrent NPC is potentially associated with fewer complications.

Conclusions: The results of our study suggest that ES for rT3-4 may be a better treatment than IMRT, but the conclusion still needs to be sought by designing more studies.
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http://dx.doi.org/10.3389/fonc.2021.703954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350726PMC
July 2021

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite-Induced Allergic Rhinitis.

Front Pharmacol 2021 8;12:681724. Epub 2021 Jul 8.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University and Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, China.

Macrophage migration inhibitory factor (MIF) is described as a pro-inflammatory cytokine involved in many inflammatory and allergic disorders, but the role of MIF in allergic rhinitis (AR) remains poorly clarified. The aim of this study was to investigate the association between circulating MIF levels and house dust mite (HDM)-induced AR, and evaluate MIF as a potential biomarker in reflecting disease severity and predicting the clinical response of sublingual immunotherapy (SLIT) in HDM-induced AR patients. In this study, we enrolled 160 persistent HDM-induced AR patients (AR group), including 48 mild AR patients (MAR group) and 112 moderate-severe AR patients (MSAR group), and 77 healthy controls (HC group). Circulating levels of MIF were measured by ELISA, and the relationship between MIF concentrations and disease severity was assessed. In the MSAR group, 106 patients were assigned to receive SLIT for 3 years. At the end of the study, patients were categorized into good response group and poor response group, and associations between clinical variables or biomarkers and clinical response were analyzed by the multivariate regression analysis. The concentrations of serum MIF were significantly higher in AR patients than in HCs, especially in those with MSAR. Moreover, circulating MIF levels were positively correlated with TNSS, VAS, serum HDM-specific IgE, total IgE, blood eosinophil count, and blood eosinophil percentage (all < 0.05). Eighty MSAR patients finally completed SLIT, 45 patients obtained good response, and 35 patients resulted in poor response. The serum levels of MIF were significantly lower in the good-response group than in the poor-response group ( < 0.001). The receiver operating characteristic analysis for MIF showed good accuracy for predicting clinical response of SLIT (area under the curve = 0.877, < 0.001). The multivariate regression analysis demonstrated that serum MIF was an independent factor for SLIT responsiveness. Serum MIF appeared to be an important biological indicator in reflecting disease severity and an independent predictor for clinical responsiveness of SLIT in HDM-induced AR patients.
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http://dx.doi.org/10.3389/fphar.2021.681724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296466PMC
July 2021

Identification of Novel Biomarkers for Evaluating Disease Severity in House-Dust-Mite-Induced Allergic Rhinitis by Serum Metabolomics.

Dis Markers 2021 19;2021:5558458. Epub 2021 May 19.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China.

The aim of this study was to identify differences in serum metabolomics profiles of house-dust-mite (HDM)-induced allergic rhinitis (AR) patients compared to controls and to explore novel biomarkers reflecting disease severity. Serum samples were collected from 29 healthy controls and HDM-induced 72 AR patients, including 30 mild patients (MAR) and 42 moderate to severe AR patients (MSAR). Metabolomics detection was performed, and orthogonal partial least square discriminate analysis was applied to assess the differences between AR patients and controls and for subgroups based on disease severity. These analysis results successfully revealed distinct metabolite signatures which distinguished MAR patients and MSAR patients from controls. MSAR patients also could be discriminated from MAR patients based on their metabolic fingerprints. Most observed metabolite changes were related to glycine, serine, and threonine metabolism, pyrimidine metabolism, sphingolipid metabolism, arginine and proline metabolism, and fatty acid metabolism. Levels of sarcosine, sphingosine-1-phosphate, cytidine, and linoleic acid significantly correlated with the total nasal symptom score and visual analogue scale in AR patients. These results suggest that metabolomics profiling may provide novel insights into the pathophysiological mechanisms of HDM-induced AR and contribute to its evaluation of disease severity.
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http://dx.doi.org/10.1155/2021/5558458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154289PMC
December 2021

The Role of Serum Metabolomics in Distinguishing Chronic Rhinosinusitis With Nasal Polyp Phenotypes.

Front Mol Biosci 2020 12;7:593976. Epub 2021 Jan 12.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease characterized by different clinical features and treatment responsiveness. This study aimed to compare the serum metabolomics profiles between eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) and healthy controls (HC) and explore objective biomarkers for distinguishing eCRSwNP before surgery. Serum samples were collected from 33 neCRSwNP patients, 37 eCRSwNP patients, and 29 HC. Serum metabolomics profiles were investigated by ultra-high-performance liquid chromatography-mass spectrometry. The analysis results revealed that neCRSwNP, eCRSwNP, and HC exhibited distinctive metabolite signatures. In addition, eCRSwNP could be distinguished from neCRSwNP referring to their serum metabolic profiles, and the top ten different metabolites were citrulline, choline, linoleic acid, adenosine, glycocholic acid, L-serine, triethanolamine, 4-guanidinobutyric acid, methylmalonic acid, and L-methionine, which were related to several most important pathways including arginine and proline metabolism; glycine, serine, and threonine metabolism; linoleic acid metabolism; and purine metabolism. Among these distinctive metabolites, citrulline, linoleic acid, adenosine, and 4-guanidinobutyric acid showed good predictabilities, and the serum levels of citrulline, linoleic acid, and adenosine were significantly correlated with tissue eosinophil (T-EOS) percentage and T-EOS count. eCRSwNP patients exhibited discriminative serum metabolic signatures in comparison with neCRSwNP patients and HC. These results suggested that metabolomics profiles contributed to understanding the pathophysiological mechanisms of CRSwNP and distinguishing its phenotypes.
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http://dx.doi.org/10.3389/fmolb.2020.593976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835901PMC
January 2021

Prediction of sublingual immunotherapy efficacy in allergic rhinitis by serum metabolomics analysis.

Int Immunopharmacol 2021 Jan 30;90:107211. Epub 2020 Nov 30.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China; Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China. Electronic address:

Background: Allergen-specific immunotherapy (ASIT) is currently the only therapy for allergic rhinitis (AR) that can induce immune tolerance to allergens. However, the course of ASIT is long and there is no objective biomarker to predict treatment efficacy. The present study aimed to explore potential biomarkers predictive of efficacy of AIT based on serum metabolomics profiles.

Methods: This prospective study recruited 72 consecutive eligible patients who were assigned to receive sublingual immunotherapy (SLIT). Serum samples were collected prior to SLIT and utilized to obtain metabolomics profiling by applying ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Treatment response was determined 3 years after SLIT, and patients were divided into effective group and ineffective group. Orthogonal partial least square-discriminate analysis (OPLS-DA) was performed to evaluate the metabolite differences between two groups.

Results: Sixty-eight patients completed the whole SLIT, 39 patients were categorized into effective group and 29 patients were classified into ineffective group. A total of 539 metabolites were obtained, and 197 of which were identified as known substances. Using these 197 known metabolites, the OPLS-DA results showed that effective group and ineffective group exhibited distinctive metabolite signatures and metabolic pathways. Six metabolites including lactic acid, ornithine, linolenic acid, creatinine, arachidonic acid and sphingosine were identified to exhibit good performance in predicting the efficacy of SLIT, and these metabolite changes mainly involved glycolysis and pyruvate metabolism, arginine and proline metabolism and fatty acid metabolism pathways.

Conclusion: By metabolomics analysis, we identified several serum biomarkers that can reliably and accurately predict the efficacy of SLIT in AR patients. The discriminative metabolites and related metabolic pathways contributed to better understand the mechanisms of SLIT in AR patients.
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http://dx.doi.org/10.1016/j.intimp.2020.107211DOI Listing
January 2021

Activated leukocyte cell adhesion molecule as a biomarker for disease severity and efficacy of sublingual immunotherapy in allergic rhinitis.

Int Immunopharmacol 2020 Nov 11;88:106975. Epub 2020 Sep 11.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China. Electronic address:

Background: Activated leukocyte cell adhesion molecule (ALCAM) plays an important role in T cell activation and immune response, but the role of ALCAM in allergic rhinitis (AR) remains unclear. The objective of the current study was to validate serum ALCAM as a biomarker in assessing disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in AR patients.

Methods: We recruited 40 healthy controls (HC group), 38 mild AR patients (MAR group) and 80 moderate-severe AR patients (MSAR group) in this study. Serum levels of ALCAM were determined by ELISA, and the association between ALCAM levels and disease severity was evaluated. In the MSAR group, 68 patients underwent and finished 3-years of SLIT, and were divided into effective group and ineffective group, the relationship between ALCAM levels and efficacy of SLIT was exampled.

Results: ALCAM levels were elevated in the serum of AR patients in comparison with HC. Moreover, serum ALCAM concentrations were higher in MSAR group than in MAR group and HC group, and levels of ALCAM significantly correlated with AR total nasal symptom score (TNSS) (r = 0.330, P < 0.001), visual analogue scale (VAS) (r = 0.387, P < 0.001) and serum total IgE levels (r = 0.442, P < 0.001). In the effective group, the ALCAM levels were significantly lower than in the ineffective group. Receiver operating characteristic (ROC) curve exhibited good accuracy for predicting clinical efficacy of SLIT (area under the curve = 0.805, P < 0.001).

Conclusions: The serum ALCAM maybe a novel biomarker for assessing disease severity and predicting clinical efficacy of SLIT in AR patients.
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http://dx.doi.org/10.1016/j.intimp.2020.106975DOI Listing
November 2020

Clinical Characteristics and Prognosis of Sudden Sensorineural Hearing Loss in Post-irradiated Nasopharyngeal Carcinoma Survivors.

Otol Neurotol 2020 08;41(7):e790-e794

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University & Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.

Objectives: Sudden sensorineural hearing loss (SSNHL) may occur in post-irradiated nasopharyngeal carcinoma (NPC) survivors with a rare rate. This study was conducted to evaluate the clinical characteristics and prognosis of this population.

Study Design: Retrospective cohort study.

Setting: Tertiary otology referral center.

Patients: Five hundred ninety nine SSNHL patients were recruited between January 2010 and January 2019. Patients were divided into two groups: NPC group (n = 24) and non-NPC group (n = 575).

Interventions: All SSNHL patients were diagnosed by pure tone audiometry and treated with steroids, blood flow promoting agents, and hyperbaric oxygen therapy.

Main Outcome Measures: We evaluated the clinical characteristics and prognosis of post-irradiated SSNHL and identified prognostic factors by logistic regression analysis.

Results: In the NPC group, the initial hearing threshold, contralateral hearing threshold, rate of vertigo, rate of profound hearing loss were all higher than in the non-NPC group (p < 0.05). Hearing gains and the rate of good recovery (both complete recovery and partial recovery) were lower in the NPC group than in the non-NPC group (p < 0.05). Logistic regression analysis revealed that NPC was significantly associated with poor hearing recovery (OR = 3.499, p = 0.040), and that a higher initial hearing threshold and longer treatment delay time were related to a poor prognosis (p < 0.05).

Conclusions: SSNHL occurred in post-irradiated NPC survivors often suffered a severe hearing loss with a high rate of accompanying vertigo. NPC may have an adverse impact on the prognosis of SSNHL, and higher initial hearing threshold and longer treatment delay time were indicators of poor hearing recovery.
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http://dx.doi.org/10.1097/MAO.0000000000002701DOI Listing
August 2020

Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons.

Neurotox Res 2017 Nov 27;32(4):603-613. Epub 2017 Jun 27.

Department of Otolaryngology Head and Neck Surgery, Xiang Ya Hospital, Central South University, Changsha, Hunan, 410013, China.

Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life-threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants. In both adult and postnatal day 3 cultures, hair cell damage began at the base of the cochleae and progressed toward the apex in a dose-dependent manner. In postnatal day 3 cultures, spiral ganglion neurons were rapidly destroyed by kanamycin prior to hair cell loss. In contrast, adult spiral ganglion neurons were resistant to kanamycin damage even at the highest concentration, consistent with in vivo models of delayed SGN degeneration. In postnatal day 3 cultures, kanamycin preferentially damaged type I spiral ganglion neurons, whereas type II neurons were resistant. Spiral ganglion degeneration of postnatal day 3 neurons was associated with upregulation of the superoxide radical and caspase-3-mediated cell death. These results show for the first time that kanamycin is toxic to postnatal day 3 spiral ganglion neurons, but not adult neurons.
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http://dx.doi.org/10.1007/s12640-017-9773-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711550PMC
November 2017

Overexpression of N-cadherin and β-catenin correlates with poor prognosis in patients with nasopharyngeal carcinoma.

Oncol Lett 2017 Mar 25;13(3):1725-1730. Epub 2017 Jan 25.

Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

An increasing amount of evidence demonstrates that epithelial-mesenchymal transition (EMT) is important in tumor invasion and metastases. The cell-cell adhesion molecule N-cadherin and the Wnt/β-catenin cascade protein β-catenin are two biomarkers of EMT. The present study aimed to measure the expression levels of N-cadherin and β-catenin in samples from patients with nasopharyngeal carcinoma (NPC) and evaluate their prognostic significance. N-cadherin and β-catenin mRNA was evaluated using reverse transcription-quantitative polymerase chain reaction in 26 NPC tissue samples and 8 nasopharyngeal epithelium samples. Protein expression of N-cadherin and β-catenin was also detected using immunohistochemistry in 128 archival NPC paraffin-embedded specimens. Finally, associations between clinical pathological parameters and prognostic values in NPC were evaluated. The results demonstrated that both the mRNA and protein levels of N-cadherin and β-catenin were significantly increased in NPC tissues compared with the controls. Enhanced expression of N-cadherin and β-catenin protein was strongly correlated with the status of lymph node metastasis and clinical stages in patients with NPC. Notably, high expression of N-cadherin and β-catenin proteins was significantly correlated with lower overall survival (OS) rate in patients with NPC. Finally, multivariate analysis demonstrated that expression of N-cadherin protein and clinical stages were independent prognostic factors for patients with NPC. Therefore, the present study demonstrated that N-cadherin and β-catenin expression may be used as potential prognostic biomarkers for patients with NPC.
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http://dx.doi.org/10.3892/ol.2017.5645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403301PMC
March 2017

Characteristic anatomical structures of rat temporal bone.

J Otol 2015 Sep 14;10(3):118-124. Epub 2015 Nov 14.

Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, NY 14214, USA.

As most gene sequences and functional structures of internal organs in rats have been well studied, rat models are widely used in experimental medical studies. A large number of descriptions and atlas of the rat temporal bone have been published, but some detailed anatomy of its surface and inside structures remains to be studied. By focusing on some unique characteristics of the rat temporal bone, the current paper aims to provide more accurate and detailed information on rat temporal bone anatomy in an attempt to complete missing or unclear areas in the existed knowledge. We also hope this paper can lay a solid foundation for experimental rat temporal bone surgeries, and promote information exchange among colleagues, as well as providing useful guidance for novice researchers in the field of hearing research involving rats.
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http://dx.doi.org/10.1016/j.joto.2015.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002576PMC
September 2015

Standardized surgical approaches to ear surgery in rats.

J Otol 2015 Jun 26;10(2):72-77. Epub 2015 Sep 26.

Center for Hearing and Deafness, University of New York at Buffalo, Buffalo, NY 14214, USA.

Objective: To describe several approaches of ear surgeries for experimental studies in rats.

Methods: Anesthetized rats were prepared for demonstration of various ear surgery approaches designed to optimize experimental outcomes in studies with specific goals and exposure requirements. The surgical approaches included the posterior tympanum, superior tympanum, inferior tympanum and occipital approaches.

Results: The middle ear cavity and inner ear were successfully exposed from different angles via the mentioned surgical approaches. For example, electrode placement for recording of cochlear bioelectric responses was easily achieved through the posterior tympanum or inferior tympanum approach. Alternatively, drug delivery or gene transfection via round window membrane was most easily accomplished using the posterior tympanum approach. Cochlear perfusion of protective or ototoxic drugs was best performed using the inferior tympanum approach. Ossicular chain interruption to induce a prolonged conductive hearing loss was readily achieved using a superior tympanum approach. Lastly, surgical destruction of the endolymphatic sac to induce experimental endolymphatic hydrops was readily performed via an occipital surgical approach.

Conclusion: These standardized surgical approaches can be applied in scientific studies of the ear with different purposes covering electrophysiology, conductive hearing loss, intra-cochlear drug perfusion and experimental studies relevant to Meniere's disease.
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http://dx.doi.org/10.1016/j.joto.2015.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002556PMC
June 2015

Standardization of experimental animals temporal bone sections.

J Otol 2015 Jun 1;10(2):66-71. Epub 2015 Oct 1.

Center for Hearing and Deafness, Department of Communicative Disorders and Sciences, University of New York at Buffalo, Buffalo, NY 14214, USA.

Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation, decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.
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http://dx.doi.org/10.1016/j.joto.2015.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002569PMC
June 2015
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